Dr. Baeten said the clinical benefits “were observed both in patients who were anti-TNF naive and patients who had not previously responded” and that there were no important safety concerns with the treatment.”
New Antigen in RA Complex
Jeremy Sokolove, MD, the VA Palo Alto Healthcare System and Stanford University, Calif., presented results of research (Abstract 815) that found histone citrullination increases innate immunostimulatory capacity and immune complexes containing citrullinated histones activate macrophage cytokine production.
Anticitrullinated protein antibodies (ACPAs) are characteristic to RA, Dr. Sokolove said, but their presence years before the onset of clinical RA has been perplexing. Even though multiple putative citrullinated antigens have been identified, including citrullinated products of NETosis, no studies have previously demonstrated their capacity to initiate RA.
Over 90% of RA patients have anti-cH2B antibodies and over half have measurable levels of synovial fluid H2B immune complexes. Dr. Sokolove said the research demonstrated that autoimmunity to cH2B is arthritogenic, both by primary immunization and immune serum transfer, but only in the setting of underlying low-grade articular inflammation.
“Our findings suggest that intra-articular histone citrullination can link innate immunity via NETosis and adaptive immunity via generation of citrullinated histone immune complexes.” Generation of citrullinated histone antigens during low-grade articular inflammation provides a potential mechanism for conversion from asymptomatic ACPA seropositivity to clinical RA, he concluded.
New Periodic Fever Syndrome
Angeliki Giannelou, MD, the National Institute for Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., reported on research (Abstract 816) that used whole exome sequencing and candidate gene screening to examine an unexplained autoinflammatory disease. The research identified a new periodic fever syndrome that is caused by missense mutations in an essential and ubiquitously expressed gene, the TRNT1 on chromosome 3.
The gene mutations were found in children from unrelated families with different ancestries. The five children had recurrent episodes of high fevers with negative sepsis work-up that included an association with microcytic anemia and a spectrum of multisystem features. The accompanying neurologic involvement ranged from mild developmental delay to nystagmus, hypotonia, optic nerve atrophy, and sensorineural hearing loss. Other manifestations included dysmorphic features, musculoskeletal and gastrointestinal symptoms, B cell immunodeficiency and hypogammaglobulinemia.
The research, Dr. Giannelou said, should allow for “further understanding of the mechanisms underlying inflammation.”
Kathy L. Holliman, MEd, is a medical writer based in Beverly, Mass.
